developlment delay and mulscular dystrophy

Question 1

Diagnostic Assessments?

Answer 1

FBC (and perhaps Fe, HbH inclusions)
Creatine kinase (CK)
Thyroid function
Amino acids
Chromosome analysis
Urine screen for MPS/Oligosaccharide disorders
Fragile X syndrome type A (FRAXA)
? TORCH, ? Pb, ? Other …

Imaging – MRI etc
Metabolic – organic acids, lactic acid, fatty acids, ammonia, uric acid, transferrins, …
Lysosomal enzymes for storage disorders
Further chromosomal investigations
Skin biopsy (for somatic mosaicism)
Microdeletions (inc. subtelomeric regions)
CGH microarray
EEG

Question 2

Major muscular dystrophy?

Answer 2

• Duchenne and Becker muscular dystrophy

Xp21, dystrophin-related

• Myotonic dystrophy (AD)

mRNA processing and transport involved

• Facio-scapulo-humeral dystrophy (AD)

7q subtelomeric involvement

• Autosomal limb-girdle muscular dystrophies

AR, AD

• Emery-Dreifuss muscular dystrophy

X-linked or AD; nuclear membrane involvement

Question 3

dmd AND BMD INFO?

Question 4

IF SEVERELY EFFECTED DYSTRPHY CONSIDER?

Question 5

MYOTONIC DYSTROPHY GENES AND SYMPTOMS?

Answer 5

CTG triplet repeat expansion >~50 (normal <38) with meiotic instability and anticipation
3’ UTR region of DMPK on 19q =>
(i) (CUG)n in mRNA => toxic effects
(ii) effect on neighbouring genes (incl SIX5)
1 in 8,000
Multi-organ disease
Muscle (facial, skeletal, smooth), and motor development
Cardiac; cataracts; endocrine – diabetes mellitus; cognitive impairment; frontal balding;

Question 6

Muscle disease 1?

Question 7

Muscle disease 2?

Answer 7

Other proteins
nuclear, mitochondrial, contractile, other
Protein storage
Desmin, ‘amyloid’, …
Secondary diseases
Inflammatory/autoimmune, immunologiocal, infectious, systemic, toxic